{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:30:21Z","timestamp":1790069421233,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Both the A194T and a quadruple mutation CYEI (S106C, H126Y, D134E and L269I) in hepatitis B virus (HBV) polymerase reverse transcriptase domain (pol\/RT) are suggested to be associated with treatment failure with tenofovir disoproxil fumarate (TDF). To further evaluate this assertion, the prevalence of these mutations at baseline as well as their development and\/or loss during TDF and tenofovir alafenamide (TAF) treatment was analysed in 3886 patients enrolled in Gilead HBV clinical studies. In total, six out of 3886 (0.2%) patients carried the rtA194T mutation, while only 1 patient carried a triple CYE and 2 patients carried a quadruple CYEI mutation at baseline. All the patients harbouring rtA194T or CYE\/CYEI at baseline achieved viral suppression by week 96 after TDF or TAF treatment. No patients developed an rtA194T mutation or\u00a0&gt;\u00a01 substitution of CYEI, and the number of patients losing any substitutions of CYEI (n\u00a0=\u00a017) was similar to the number who developed a single substitution of CYEI (n\u00a0=\u00a032) during treatment. Phenotypic evaluation of the site\u2010directed mutant (SDM) panel containing these mutations with or without other resistance mutations did not demonstrate a significant shift in TFV and TAF potency in vitro. No evidence of rtA194T and CYEI conferring resistance to TDF or TAF was observed based on the treatment responses to TDF or TAF in patients with mutations at baseline, the lack of selection of mutations after starting TDF or TAF treatment and no change in susceptibility to TFV or TAF in vitro.<\/jats:p>","DOI":"10.1111\/jvh.13397","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T07:30:17Z","timestamp":1600673417000},"page":"30-39","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of Hepatitis B virus polymerase mutations A194T and CYEI and tenofovir disoproxil fumarate or tenofovir alafenamide resistance"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-2009","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Virology Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Chang","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Martin","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Mo","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becket","family":"Feierbach","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200205303462202"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.09.033"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.09.020"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22414"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.10.026"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22841"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12613"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03845-14"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.028"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308435"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.223206"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.11.024"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(16)30107-8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(16)30024-3"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01064-18"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","unstructured":"ChanHLY MarcellinP PanCQ et al. No resistance to tenofovir alafenamide detected through 144 weeks of treatment in patients with chronic Hepatitis B[Poster 386]. AASLD: The Liver Meeting\u00ae 2018; November 9\u201013 2018;San Francisco CA.","DOI":"10.1136\/gutjnl-2018-IDDFabstracts.207"},{"issue":"6","key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1177\/135965350501000612","article-title":"Selection of hepatitis B virus polymerase mutations in HIV\u2010coinfected patients treated with tenofovir","volume":"10","author":"Sheldon J","year":"2005","journal-title":"Antivir Ther"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22790"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00138-06"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12223-018-0650-z"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.02.006"},{"key":"e_1_2_7_23_1","unstructured":"LiuY ChenR LiX et al. The rtS106C+H126Y+D134E triple variant of hepatitis B virus has no direct association with tenofovir resistance in Chinese patients[Poster ID 589]. Asian Pacific Association for the Study of Liver; February 20\u201024 2019;Manila Philippines."},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2003.07.003"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.12.012"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4398"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.07.010"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.13397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.13397","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T07:59:01Z","timestamp":1693209541000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/jvh.13397"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13397","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,24]]},"assertion":[{"value":"2020-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}